Mannello Ferdinando, Medda Virginia, Smaniotto Alessandra, Tonti Gaetana A
a Department of Biomolecular Sciences, Section of Clinical Biochemistry, Faculty of Sciences and Technologies, University 'Carlo Bo', Via O. Ubaldini 7, 61029 Urbino (PU), Italy.
b Department of Biomolecular Sciences, Section of Clinical Biochemistry, Faculty of Sciences and Technologies, University "Carlo Bo", Via O. Ubaldini 7, 61029 Urbino (PU), Italy.
Expert Rev Endocrinol Metab. 2009 Sep;4(5):493-505. doi: 10.1586/eem.09.28.
Breast cancer, a complex and multifactorial disease, is the most commonly diagnosed malignancy affecting women. Methods currently available for breast cancer detection have well-described limitations; in this respect, the intraductal approaches directly assess the microenvironment of the breast. Nipple aspirate fluid (NAF) can be noninvasively obtained from the breast in most women and represents a promising biological tool to assess metabolic, hormonal and molecular changes occurring in the cells lining the ducts, from which breast cancer arises. The aim of this review is to highlight the application of NAF studies in the field of biomarker discovery, which provide results useful for early detection and prevention of breast cancer risk; in fact, the analysis of NAF (mirroring the ductal-lobular microenvironment) is a reliable method for assessment of metabolic/hormonal pathways within the mammary gland, identifying biomolecular mechanisms of breast cancer initiation and progression. The intracrinology of breast microenvironment (i.e., hormonal status in NAF) may provide independent diagnostic/prognostic factors, highlighting the importance of early altered hormonal metabolism (e.g., aromatase, estrogen sulfotransferase and steroid sulfatase pathway) in relation to breast cancer initiation. The possible application of targeted therapies through the inhibition of intratumoral enzymes involved in steroid metabolism is also discussed. The intraductal approach to hormone analyses may provide a further panel of biomarkers providing clinical benefits and strengthening the armory against breast cancer.
乳腺癌是一种复杂的多因素疾病，是女性中最常被诊断出的恶性肿瘤。目前可用于乳腺癌检测的方法存在诸多已被充分描述的局限性；在这方面，导管内方法可直接评估乳房的微环境。大多数女性都可以通过非侵入性方法从乳房获取乳头抽吸液（NAF），它是一种很有前景的生物学工具，可用于评估乳腺导管内衬细胞中发生的代谢、激素和分子变化，而乳腺癌正是起源于这些细胞。本综述的目的是强调NAF研究在生物标志物发现领域的应用，这些研究结果对乳腺癌风险的早期检测和预防很有用；事实上，对NAF（反映导管 - 小叶微环境）的分析是评估乳腺内代谢/激素途径的可靠方法，能够识别乳腺癌发生和发展的生物分子机制。乳腺微环境的内分泌学（即NAF中的激素状态）可能提供独立的诊断/预后因素，凸显了早期激素代谢改变（如芳香化酶、雌激素硫酸转移酶和类固醇硫酸酯酶途径）与乳腺癌发生的相关性。本文还讨论了通过抑制参与类固醇代谢的肿瘤内酶进行靶向治疗的可能性。导管内激素分析方法可能会提供更多的生物标志物，带来临床益处并增强对抗乳腺癌的手段。
